Kuchroo V K, Das M P, Brown J A, Ranger A M, Zamvil S S, Sobel R A, Weiner H L, Nabavi N, Glimcher L H
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115.
Cell. 1995 Mar 10;80(5):707-18. doi: 10.1016/0092-8674(95)90349-6.
CD4 T helper precursor cells mature along two alternative pathways, Th1 and Th2. Here we show that these pathways are differentially activated by two costimulatory molecules, B7-1 and B7-2. Using anti-B7 antibodies, this developmental step was manipulated both in vitro and in vivo in experimental allergic encephalomyelitis (EAE). Anti-B7-1 reduced the incidence of disease while anti-B7-2 increased disease severity. Neither antibody affected overall T cell induction but rather altered cytokine profile. Administration of anti-B7-1 at immunization resulted in predominant generation of Th2 clones whose transfer both prevented induction of EAE and abrogated established disease. Since co-treatment with anti-IL-4 antibody prevented disease amelioration, costimulatory molecules may directly affect initial cytokine secretion. Thus, interaction of B7-1 and B7-2 with shared counterreceptors CD28 and CTLA-4 results in very different outcomes in clinical disease by influencing commitment of precursors to a Th1 or Th2 lineage.
CD4辅助性T细胞前体细胞沿着两条不同的途径成熟，即Th1和Th2途径。我们在此表明，这两条途径分别由两种共刺激分子B7-1和B7-2以不同方式激活。利用抗B7抗体，在实验性自身免疫性脑脊髓炎（EAE）的体外和体内实验中对这一发育步骤进行了调控。抗B7-1降低了疾病的发病率，而抗B7-2则增加了疾病的严重程度。两种抗体均未影响整体T细胞的诱导，而是改变了细胞因子谱。在免疫时给予抗B7-1导致主要产生Th2克隆，其转移既能预防EAE的诱导，又能消除已建立的疾病。由于与抗IL-4抗体共同处理可阻止疾病改善，共刺激分子可能直接影响初始细胞因子的分泌。因此，B7-1和B7-2与共同的反受体CD28和CTLA-4的相互作用，通过影响前体细胞向Th1或Th2谱系的分化，在临床疾病中导致非常不同的结果。
